A growing body of evidence indicates that angiogenesis is essential to the progression of cancer. Angiogenesis is the sprouting of new capillaries from preexisting blood vessels. Normally, angiogenesis in mammals is confined to the reproductive system, embryogenesis and development, and repair after injury. Angiogenesis can also occur, however, in pathological conditions such as cancer, retinal neovascularization, neovascularization in atherosclerotic plaques, hemangiomas, arthritis, and psoriasis. Without vascularization, tumors may remain for years as small (less than a few millimeters) asymptomatic lesions. Angiogenesis allows the cancerous cells access to the circulatory system. The new blood vessels provide a gateway for cancer cells to enter the circulation and metastasize to distant sites.
Site specific expression of E-selectin on endothelial cells occurs during cancerous and inflammatory conditions, and may represent an early stage in the pathogenesis of these conditions.
Tumor vascular drug-targeting strategies aimed at blocking the tumor blood flow have enormous therapeutic potential in inhibiting tumor growth and reducing tumor mass. Current methods of cancer therapy that focus on the vascular needs of the tumor have relied on the use of anti-angiogenic factors, which prevent the formation of new blood vessels and inhibit new tumor growth in regions of neovascularization. This approach, however, does little to eliminate areas in existing tumors where mature vessels supply adequate circulation or peripheral regions of tumors that share vascularization with adjacent normal tissues.
There remains a need for effective targeting of existing tumor vasculature and thereby an effective cancer therapy, as well as targeting effective therapeutics to other diseases associated such as inflammatory conditions involving the selectins.